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PubMed1981

[Problems in designing a protocol for a leprosy vaccine trial. (author's transl)].

Investigations carried out by the Scientific Working Group on Immunology of Leprosy (IMMLEP) have led to the planning of field trials of an experimental vaccine preparation to be carried out in few years' time. The objectives of these trials have been defined as follows: 1) The main objective should be the assessment of the protective effect of the vaccine against leprosy, its various forms and more particularly the lepromatous form. 2) Another important objective will be to determine the value and significance of the greatest possible number of immunological tests as indicators of sensitization and as preliminary indicators of protection against leprosy, its various forms and more particularly the lepromatous form. The protocol of the trials should take into account the following points: 1) In view of the uneven distribution of leprosy, the variations in the distribution of its various forms, as well as the unknown epidemiological factors, several trials should be planned with at least one in a country in Asia or Africa and one in a country in Latin America. 2) Because of the long incubation of leprosy and its occurrence at any age, all age groups should be included in the trials. 3) To take into account the low incidence of leprosy, the trials should involve a large population and the observation period should last about ten years. 4) In view of the low incidence of leprosy and its uneven distribution, the random sampling for allocation to vaccinated and control groups should be based on individuals. 5) Because of the absence of objective criteria for the diagnosis of leprosy, provision should be made in the protocol to minimize over- and under-diagnosis. 6) When the immunological tests to ber studied within the protocol itself may affect the results of the trial, special groups should be planned for these investigations.

Adolescent↗
PubMed1980

Risks of treating leprosy in a general hospital.

The Christian Medical College and Hospital, Vellore, with 1208 beds, is situated in an endemic area in which the prevalence of leprosy among adults is 3.4%. Two percent of the beds are occupied by leprosy patients, and about 4000 are seen as outpatients per year. They share with other patients all medical, nursing, laboratory, and other services. The impact of these attitudes and practices on the incidence of leprosy among staff and students was studied. This hospital has 2665 staff, including housekeeping personnel, technicians, nurses, and doctors. There are 777 medical, nursing, and paramedical students. Every employee and student is screened prior to entry into this institution and subjected to routine annual examinations. Of those who at initial screening had no evidence of leprosy, 24 acquired the disease. Sixteen had tuberculoid, two borderline, and six indeterminate leprosy. The attack rate of 0.7% is significantly lower than the incidence or prevalence of leprosy in the area. Factors contributing to this low attack rate are discussed with particular reference to age, sex, educational background, residential status, and area of work. It is suggested that staff and students serving leprosy patients for whom no isolation is practiced do not carry any additional risk of acquiring clinical leprosy.

Adolescent↗
PubMed1995

The genetic epidemiology of leprosy in a Brazilian population.

Data on leprosy patients have been obtained from the Dispensary of Leprosy of Campinas, São Paulo, where records on practically all cases of leprosy in the Campinas area during the period 1960-70 are filed. The whole sample comprises 10,886 individuals, distributed among 1,568 families. Complex segregation analysis was utilized to determine the nature of the genetic factors that may operate on leprosy and its subtypes. The results suggest the presence of a recessive major gene controlling susceptibility to leprosy per se, with frequency of approximately .05, although there are deviations from the expected Mendelian segregation proportions. Possible etiologic heterogeneity was examined by considering two subtypes separately: for lepromatous leprosy and tuberculoid leprosy there are suggestions for a segregating major effect; however, Mendelian transmission could not be demonstrated in either case. Therefore, there is no evidence to suggest unique genetic determinants for leprosy subtypes.

Adolescent↗
PubMed1994

Decreased beta-amyloid and increased abnormal Tau deposition in the brain of aged patients with leprosy.

We examined the brains of 37 leprosy patients (mean age, 76.3 +/- 7.8 years), 5 patients with Alzheimer-type dementia (mean age, 79.0 +/- 9.5 years), and 23 age-matched non-dementia controls (mean age, 77.6 +/- 5.4 years). The frequency of beta-amyloid (A beta)-positive cases was lower (27.0%) in leprosy patients (n = 37) than in controls (47.8%; P = 0.05, Z = 1.49). When senile plaque subtypes were examined, type III (classical) plaques were significantly fewer (P < 0.05) in leprosy subjects compared with controls. Interestingly, neurofibrillary tangles in the temporal cortex were much more frequent in leprosy patients than in controls (P < 0.05). However, hippocampal CA3 pyramidal neurons in leprosy patients were well preserved. These data indicate that 1) leprosy patients have a low risk of A beta deposition but a high risk of abnormal tau deposition, 2) abnormal tau deposition is unrelated to A beta deposition in leprosy, and 3) neuronal loss is unrelated to abnormal tau deposition. It is not clear at present whether the result is related to the disease process itself, antileprosy treatment, environmental factors, or the genetic background in leprosy patients.

Aged↗
PubMed1993

Bophuthatswana's contribution towards the elimination of leprosy as a public health problem in southern Africa by the year 2000.

Before independence in December 1977, the control of leprosy in Bophuthatswana was conducted by specialized centres such as Mjanyana, Mkambati, Westfort, etc in the Republic of South Africa. As a result of this 'verticalization', very few cases of leprosy were diagnosed and treated in the general and/or community hospitals. Professional awareness of the disease in these institutions decreased and stigmatization of its sufferers by the community increased. In 1989, the first leprosy control programme based on the multidrug therapy as recommended by the World Health Organization was jointly launched by the Leprosy Mission of Southern Africa and the Bophuthatswana Department of Health and Social Services. The initial leprosy database for the programme was provided by the review of the medical records at Westfort Hospital (the only leprosy referral centre in the region) from 1973 to 1988 (15 years). This article reviews the epidemiologic course of leprosy in Bophuthatswana as it has evolved over the last 15 years, prior to the launching of the programme in 1989, and assesses the impact of the newly introduced control measures on the intended elimination of leprosy as a public health problem in the region by the year 2000.

Adolescent↗
PubMed1996

Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Karonga Prevention Trial Group.

BACKGROUND: Repeat BCG vaccination is standard practice in many countries for prevention of tuberculosis and leprosy, but its effectiveness has not been evaluated. The addition of Mycobacterium leprae antigens to BCG might improve its effectiveness against leprosy. A double-blind, randomised, controlled trial to evaluate both these procedures was carried out in Karonga District, northern Malawi, where a single BCG vaccine administered by routine health services had previously been found to afford greater than 50% protection against leprosy, but no protection against tuberculosis. METHODS: Between 1986 and 1989, individuals lacking a BCG scar were randomly assigned BCG alone (27,904) or BCG plus killed M leprae (38,251). Individuals with a BCG scar were randomly allocated placebo (23,307), a second BCG (23,456), or BCG plus killed M leprae (8102). Incident cases of leprosy and tuberculosis were ascertained over the subsequent 5-9 years. FINDINGS: 139 cases of leprosy were identified by May, 1995; 93 of these were diagnostically certain, definitely postvaccination cases. Among scar-positive individuals, a second BCG vaccination gave further protection against leprosy (about 50%) over a first BCG vaccination. The rate ratio for all diagnostically certain, definitely postvaccination cases, all ages, was 0.51 (95% CI 0.25-1.03, p = 0.05) for BCG versus placebo. This benefit was apparent in all subgroups, although the greatest effect was among individuals vaccinated below 15 years of age (RR = 0.40 [95% CI 0.15-1.01], p = 0.05). The addition of killed M leprae did not improve the protection afforded by a primary BCG vaccination. The rate ratio for BCG plus killed M leprae versus BCG alone among scar-negative individuals was 1.06 (0.62-1.82, p = 0.82) for all ages, though 0.37 (0.11-1.24, p = 0.09) for individuals vaccinated below 15 years of age. 376 cases of postvaccination pulmonary tuberculosis and 31 of glandular tuberculosis were ascertained by May, 1995. The rate of diagnostically certain tuberculosis was higher among scar-positive individuals who had received a second BCG (1.43 [0.88-2.35], p = 0.15) than among those who had received placebo and there was no evidence that any of the trial vaccines contributed to protection against pulmonary tuberculosis. INTERPRETATION: In a population in which a single BCG vaccination affords 50% or more protection against leprosy, but none against tuberculosis, a second vaccination can add appreciably to the protection against leprosy, without providing any protection against tuberculosis.

Adolescent↗
PubMedDate not supplied

Susceptibility to leprosy and serum atypical pseudocholinesterase.

The pseudocholinesterase levels and the nature of the enzyme as shown by the dibucaine number (D.N.) were estimated in 720 controls and 420 lepromatous leprosy patients, and 301 tuberculoid leprosy patients. There was no statistical difference in the esterase levels between leprosy patients and normal controls. But the distribution of D.N. was significantly different in the leprosy patients compared to the normal population studied. The D.N. below 40 indicates the samples with the atypical pseudocholinesterase--the presence of which is genetically determined. The distribution of samples with D.N. below 40 was significantly higher in the lepromatous leprosy patients compared to the normal population or tuberculoid leprosy patients. It is proposed that since there is a greater incidence of the atypical enzyme in lepromatous leprosy cases, the presence of this enzyme or the deficiency of the typical enzyme may make a person more susceptible to leprosy.

Adolescent↗
PubMed1989

Leprosy survey in industries in Bombay.

Population surveys for leprosy in industrial cities like Bombay revealed that about 60% of adult subjects especially males could be examined. The fact that the prevalence rate of leprosy particularly multibacillary type is much higher in this segment of population as compared to other groups indicates the importance of examining this population at their workspot like industries. 22287 industrial workers were examined for leprosy by paramedical auxiliaries in their establishments and 270 leprosy cases were detected (P.R. 12/1000). However, only 13 multibacillary cases (P.R. 0.5/1000) could be unearthed. 12 patients were with grade II and above. 184 (83%) were untreated. 161 (60%) patients reported for treatment. With available resources, case holding of patients who are not within the control area of the project becomes a challenging job for paramedical workers though large number of leprosy cases are detected amongst industrial workers. If industrial management arranges treatment for leprosy patients without dislocating them from their service, the pool of infection in the urban community will be reduced and can contribute tremendously towards urban leprosy control programme.

Humans↗
PubMed2002

Associations between human leukocyte antigens and leprosy in the Turkish population.

Leprosy is a chronic infection caused by an intracellular microorganism. Genetic predisposition to both disease susceptibility and to host immunological response has been postulated for many years. The aim of this study was to determine whether there is HLA-linked susceptibility to leprosy and its different types. HLA-class I (A, B, C) and II (DR, DQ) antigen frequencies in 80 patients with leprosy (35 borderline lepromatous, 25 lepromatous, 15 borderline tuberculoid, five tuberculoid) were compared with those in 120 healthy individuals. HLA-class I antigens A9, A10, A32, B5, B21, Bw4, Bw6, Cw1, Cw2 and HLA-class II antigens DR9, DR10, DRw52, DQ1, DQ3 were found to be significantly more frequent in patients with leprosy, whereas HLA-class I antigens A3, B44, B49 and HLA-class II antigen DQ5 were so in controls. However, there was no significant difference in HLA-class I and II antigen frequencies between subtypes of leprosy. HLA-A null antigen was found to have weak expression in patients with leprosy. In conclusion, factors other than HLA-class I and class II antigens may have a more critical role in the pathophysiology of leprosy infection in man.

Adult↗
PubMed1989

Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers.

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

ABO Blood-Group System↗
PubMed1989

Hepatitis B antigen and antibody in patients with leprosy: a study of three resettlement villages in Thailand.

It remains uncertain whether the cellular immune abnormalities of patients with lepromatous leprosy interfere with resolution of hepatitis B virus (HBV) infections. To investigate this question in an area coendemic for the two diseases, we determined the prevalence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in: 1) 204 leprosy patients living in three leprosy resettlement villages; 2) 198 contacts living in the same villages; and 3) 44 newly diagnosed leprosy patients in Thailand. Within the villages, the prevalence of HBsAg positivity was inversely related to age, tended to be more frequent in patients with tuberculoid than lepromatous leprosy, and was similar after age adjustment among persons with and without leprosy. The prevalence of HBV markers found in newly diagnosed patients was similar to that in the villagers. We conclude that extensive HBV transmission had occurred in the resettlement villages and that the natural history of HBV infection was similar in persons with, whether tuberculoid or lepromatous, and without leprosy.

Adolescent↗
PubMed2001

Utility of fine-needle aspiration cytology in the classification of leprosy.

The role of fine-needle aspiration cytology (FNAC) in the diagnosis of benign skin lesions has been restricted primarily to the evaluation of bacteriologic and morphologic indices in leprosy. This study was undertaken to evaluate the efficacy of FNAC in the diagnosis and classification of lepromatous lesions. Aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial load was determined by modified Ziehl-Neelsen (ZN) stain. A skin biopsy was taken from the same site at the same sitting. Frozen and paraffin sections stained with hematoxylin-eosin (H&E) and ZN stains were examined from the biopsy specimen. In 61 of 94 cases (64.9%), the aspirates were satisfactory. Both diagnosis and classification of leprosy were possible in 40 of these 61 cases; the rest of the aspirates showed nonspecific chronic inflammation. The 39 cases of leprosy where a biopsy was available from the same site were classified on FNAC into tuberculoid (TT and BT), lepromatous (LL and BL), and midborderline (BB) subtypes. Taking the histologic diagnosis and Ridley-Jopling classification to be the gold standard, a strong concordance in tuberculoid leprosy cases (18 of 20 cases, 90%) and in lepromatous cases (15 of 16 cases, 93.7%) was observed. Midborderline cases of leprosy posed a problem, and a correct cytohistological correlation was observed in only one of the three cases.

Adolescent↗
PubMed1992

Serum tumor necrosis factor and interleukin 1 in leprosy and during lepra reactions.

Tumor necrosis factor--alpha (TNF), one of the mediators of septic shock, has a role in the immunopathological complications of several infections. However, its role in leprosy is yet unclear. In this study, serum TNF and IL-1 levels in 64 patients spread over the spectrum of leprosy [lepromatous leprosy (LL), 30; borderline lepromatous, 12; borderline borderline, 8; and borderline tuberculoid-tuberculoid leprosy, 14] were measured at the time of admission. Elevated levels of TNF ranging from 15 to 4500 pg/ml were detected in lepromatous leprosy cases (399 +/- 189) and low levels ranging from 15 to 160 pg/ml were detected in the tuberculoid form of leprosy. Patients undergoing type 1 and type 2 lepra reactions also exhibited high TNF levels of 15-2100 pg/ml. Of the 14 clinically healthy individuals studied, 3 showed TNF levels of 15, 50, and 58 pg/ml. Interleukin 1-beta (IL-1) levels were found to be significantly higher in LL cases (70-5000 pg/ml) (328 +/- 184) in comparison to other groups or normal controls (9 +/- 3). The coefficient of correlation between TNF and IL-1 levels was statistically significant in LL and reaction cases (r = 0.96, P less than 0.001). These patients were followed up as outpatients for a period of 1 year. It was observed that 4 out of 8 patients with TNF levels greater than 100 pg/ml went into lepra reactions between 2 and 6 months after entry into the study, whereas only 5 out of 56 with less than 100 pg/ml went into mild lepra reactions (chi 2 = 9.7, P less than 0.01). Determination of TNF and IL-1 levels thus seems to have a prognostic significance in terms of lepra reaction in patients.

Adolescent↗
PubMed1991

Impairment of fingertip vasomotor reflexes in leprosy patients and apparently healthy contacts.

Fingertip blood-flow velocity and its control by vasomotor reflexes were studied in leprosy patients and in healthy controls with a laser Doppler flowmeter. In newly registered patients, the flow was significantly lower than in the healthy controls, and even lower values were recorded in the long-standing patients with lower limb ulcers and/or deformity. The newly registered patients showed substantially impaired vasomotor reflex responses in the fingertips to cold challenge of the opposite hand or deep inspiratory gasp. Low blood flow and impairment of vasomotor reflexes were more prominent in those leprosy patients who showed clinical evidence of neuropathy and/or histological evidence of reaction in a punch biopsy of leprosy skin lesions. This aspect of dysautonomia to cold challenge was particularly prominent in apparently healthy, fully treated ex-patients. There was an unexpectedly high prevalence of impairment of vasomotor reflexes in newly registered and apparently healthy, adequately treated leprosy patients. The method is very sensitive, and it remains to be established whether the lesions it detects are nonprogressive residues, or previous nerve damage, or an indication of on-going nerve damage. A minority of leprosy contacts showed impairment of vasomotor reflexes. Those with two or more affected fingers were more likely to have had a higher level of exposure to Mycobacterium leprae than those with one or no affected fingers. The cause of this unexpected impairment of fingertip vasomotor reflexes in a minority of leprosy control workers has not yet been determined.

Adolescent↗
PubMed1991

Mycobacterial flora of the skin in leprosy.

The presence of mycobacteria on the skin of healthy people and in leprosy lesions has been documented previously. The present study observed the mycobacterial flora on the hands (by the hand-washing method) and fingers (by the inoculated culture medium using scraped material obtained during the preparation of slit-skin smears) in 89 untreated leprosy patients. We also evaluated the slit-skin smears from fingers for the diagnosis of leprosy. In 16 patients (17.9%) mycobacteria were cultured from scrapings and hand washings. The frequency of isolates from lepromatous (LL) leprosy cases (52.9%) was significantly higher than from tuberculoid (TT) leprosy cases (5.2%). It was observed that Mycobacterium avium and M. scrofulaceum were the only opportunistic mycobacteria isolated from multibacillary patients, and two hypotheses are discussed to explain these findings. The slit-skin smears from fingers were as satisfactory as smears from other sites for the diagnosis of leprosy, but they were less satisfactory for estimating the morphological index.

Humans↗
PubMed1997

Associations between HLA-DRB1 alleles and leprosy in an Indonesian population.

To investigate whether the susceptibility to leprosy (type), subclinical infection with Mycobacterium leprae and the antibody response against M. leprae-specific antigens are associated with HLA-DR phenotypes sequence-specific oligonucleotide HLA-DRB1 and DQA1 typing and antibody assays have been performed in 79 leprosy patients (41 TT/BT and 38 LL/BL) and 50 healthy controls from a Javanese population in Yogyakarta, Indonesia. DRB1*02 was associated with LL/BL [odds ratio (OR) 2.54, 95% confidence interval (CI) 0.97-9.78, p = 0.037 and attributable risk (AR) 41.5%] but not with TT/BT leprosy (p > 0.05). HLA-DRB1*12 was negatively associated with leprosy (either LL/BL or TT/BT [OR 0.33-0.35, p < 0.05, prevented fraction (PF) 58.8%-65.3%]. No significant association was found between HLA-DRB1 or DQA1 type, anti-M. leprae antibody level and subclinical infection with M. leprae. These data indicate that in this population susceptibility to lepromatous leprosy is associated with HLA-DRB1*02, while resistance to leprosy is associated with HLA-DRB1*12. These associations are not paralleled with associations of the same HLA types with anti-M. leprae antibody level. Finally, the results of this study also support the notion that infection with M. leprae per se is not associated with HLA-DRB1 or DQA1 alleles.

Alleles↗
PubMed1984

Leprosy in a trachomatous population.

In an Egyptian leprosy hospital, 17% of 133 patients had a visual acuity of less than 3/60. Corneal opacity, phthisis bulbi, and cataract accounted for 85% of blindness. Leprosy and trachoma together produce blinding corneal opacity by exposure, leprous keratitis, and trichiasis and entropion. Inturned lids, a late result of conjunctival scarring due to childhood trachoma, were less frequent in patients with lepromatous leprosy than in patients with tuberculoid leprosy; because conjunctival scarring from trachoma depends on cell-mediated immunity, patients with lepromatous leprosy may not have had severe trachomatous scarring develop due to their lifelong abnormality in cellular immunity. In patients with leprosy, even when complicated by trachoma, simple measures to prevent or restore vision include medical treatment of leprosy, surgical correction of lid deformities, sector iridectomy for constricted pupils or central corneal opacities, and cataract extraction.

Adult↗
PubMedDate not supplied

The epidemiology of leprosy in a high prevalence village in Papua New Guinea.

In a village of about 1000 people in Papua New Guinea the prevalence of clinical leprosy was 8.6% compared to about 3% in surrounding villages. This exceptionally high prevalence could not be explained by recent introduction of the disease or by social factors. Dapsone-resistant disease and faulty compliance with treatment are considered to be contributory to persistent infectivity of old cases which, together with the presence of 20 previously undiagnosed cases, comprised a large infective source. Social ostracism of cases was not observed and the extensive social mixing of all ages would facilitate widespread dissemination of infection. A high prevalence, particularly in children, of elevated levels of IgM antibody to phenolic glycolipid-1 Mycobacterium leprae specific antigen suggests frequent subclinical infection. The greater prevalence of clinical leprosy following childhood in the village favours altered susceptibility following exposure in childhood. There was a higher prevalence of leprosy in close relatives of cases when compared with the same relatives of age and sex matched leprosy-free controls. The occurrence of familial clustering of leprosy in a hyperendemic area with intense transmission suggests that unidentified inherited factors influence susceptibility to clinical leprosy. It is suggested that the clustering of adverse inherited traits through intermarriage may explain this hyperendemic focus on leprosy.

Adolescent↗